Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model

Ann Nucl Med. 2020 May;34(5):329-336. doi: 10.1007/s12149-020-01452-z. Epub 2020 Mar 6.

Abstract

Objective: Although 2-18F-fluoro-2-deoxy-glucose (18F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of L- and D-2-18F-α-methyl-phenylalanine (2-18F-FAMP) as radiotracers; i.e., their rapid blood clearance and low renal accumulation. In the present study we evaluated the utility of L- and D-2-18F-FAMP for imaging bladder cancer in a mouse model.

Methods: We used the human bladder cancer cell line HT1376 to prepare a bladder cancer xenograft model in mice bearing both orthotopic and subcutaneous tumors. Biodistribution and PET imaging studies were performed at 1 and 3 h after injection of L-2-18F-FAMP or D-2-18F-FAMP. 18F-FDG was used as a control.

Results: At 1 h after injection, greater accumulations of both L-2-18F-FAMP and D-2-18F-FAMP were observed in the orthotopic tumors compared to 18F-FDG. The orthotopic tumor-to-muscle ratio of D-2-18F-FAMP was significantly higher than that of 18F-FDG (p < 0.01), because of the rapid blood clearance of D-2-18F-FAMP. L-2-18F-FAMP showed the highest subcutaneous tumor-to-muscle ratio (p < 0.01) due to its high subcutaneous tumor uptake. Compared to L-2-18F-FAMP, D-2-18F-FAMP exhibited faster clearance and lower kidney accumulation. In the PET imaging studies, L- and D-2-18F-FAMP both clearly visualized the orthotopic bladder tumors at 1 h after injection.

Conclusion: Our study showed that L-2-18F-FAMP and D-2-18F-FAMP have the potential to detect bladder cancer.

Keywords: Bladder cancer; F-18-labeled amino acid; Mouse model; PET imaging.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Disease Models, Animal
  • Fluorine Radioisotopes*
  • Humans
  • Isotope Labeling
  • Mice
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacokinetics
  • Positron-Emission Tomography
  • Radioactive Tracers
  • Tissue Distribution
  • Urinary Bladder Neoplasms / diagnostic imaging*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Fluorine Radioisotopes
  • Radioactive Tracers
  • alpha-methylphenylalanine
  • Phenylalanine
  • Fluorine-18